1887

Abstract

This study investigated the molecular mechanisms of carbapenem resistance in clinical isolates of from Korea and the clinical outcomes of resistant infection. Sixteen isolates showing resistance to carbapenems collected from a tertiary-care hospital were examined for the mechanisms of carbapenem resistance. PCR and sequencing experiments detected the AmpC β-lactamase gene in all 16 clinical isolates, whilst the genes of extended-spectrum β-lactamases were detected in 12 of 16 isolates. SDS-PAGE experiments indicated that all the isolates lacked the 35 kDa and/or 36 kDa outer-membrane proteins (OMPs). Sequence analysis of the corresponding OMP genes revealed various alterations. PFGE analysis demonstrated that there were no major clonal relationships among the isolates. However, multilocus sequence typing experiments showed that all isolates shared the same sequence type (ST), ST11, except for one isolate of ST48. The crude mortality rate of infected patients was 81.8 %. Carbapenem resistance was mainly due to a combination of DHA-1 AmpC β-lactamase coupled with the loss of OmpK35 and/or OmpK36 and was associated with poor clinical outcome.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.037036-0
2012-02-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jmm/61/2/239.html?itemId=/content/journal/jmm/10.1099/jmm.0.037036-0&mimeType=html&fmt=ahah

References

  1. Bae I. K., Jang S. J., Kim J., Jeong S. H., Cho B., Lee K. 2011; Interspecies dissemination of the bla gene encoding PER-1 extended-spectrum β-lactamase. Antimicrob Agents Chemother 55:1305–1307 [View Article][PubMed]
    [Google Scholar]
  2. CLSI 2007; Performance Standards for Antimicrobial Susceptibility Testing; 17th Informational Supplement. M100-17. Wayne, PA: Clinical and Laboratory Standards Institute;
  3. Crowley B., Benedí V. J., Doménech-Sánchez A. 2002; Expression of SHV-2 β-lactamase and of reduced amounts of OmpK36 porin in Klebsiella pneumoniae results in increased resistance to cephalosporins and carbapenems. Antimicrob Agents Chemother 46:3679–3682 [View Article][PubMed]
    [Google Scholar]
  4. Horan T. C., Andrus M., Dudeck M. A. 2008; CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332 [View Article][PubMed]
    [Google Scholar]
  5. Jacoby G. A., Han P. 1996; Detection of extended-spectrum β-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli. J Clin Microbiol 34:908–911[PubMed]
    [Google Scholar]
  6. Kaczmarek F. M., Dib-Hajj F., Shang W., Gootz T. D. 2006; High-level carbapenem resistance in a Klebsiella pneumoniae clinical isolate is due to the combination of blaACT-1 β-lactamase production, porin OmpK35/36 insertional inactivation, and down-regulation of the phosphate transport porin PhoE. Antimicrob Agents Chemother 50:3396–3406 [View Article][PubMed]
    [Google Scholar]
  7. Ko K. S., Yeom J.-S., Lee M. Y., Peck K. R., Song J.-H. 2008; Clonal dissemination of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolates in a Korean hospital. J Korean Med Sci 23:53–60 [View Article][PubMed]
    [Google Scholar]
  8. Lee K., Chong Y., Shin H. B., Kim Y. A., Yong D., Yum J. H. 2001; Modified Hodge and EDTA-disk synergy tests to screen metallo-β-lactamase-producing strains of Pseudomonas and Acinetobacter species. Clin Microbiol Infect 7:88–91 [View Article][PubMed]
    [Google Scholar]
  9. Lee K., Yong D., Choi Y. S., Yum J. H., Kim J. M., Woodford N., Livermore D. M., Chong Y. 2007; Reduced imipenem susceptibility in Klebsiella pneumoniae clinical isolates with plasmid-mediated CMY-2 and DHA-1 β-lactamases co-mediated by porin loss. Int J Antimicrob Agents 29:201–206 [View Article][PubMed]
    [Google Scholar]
  10. Lee K., Kim C. K., Yong D., Jeong S. H., Yum J. H., Seo Y. H., Docquier J.-D., Chong Y. 2010a; Improved performance of the modified Hodge test with MacConkey agar for screening carbapenemase-producing Gram-negative bacilli. J Microbiol Methods 83:149–152 [View Article][PubMed]
    [Google Scholar]
  11. Lee K., Kim C. K., Hong S. G., Choi J., Song S., Koh E., Yong D., Jeong S. H., Yum J. H. other authors 2010b; Characteristics of clinical isolates of Acinetobacter genomospecies 10 carrying two different metallo-β-lactamases. Int J Antimicrob Agents 36:259–263 [View Article][PubMed]
    [Google Scholar]
  12. Marchaim D., Navon-Venezia S., Schwaber M. J., Carmeli Y. 2008; Isolation of imipenem-resistant Enterobacter species: emergence of KPC-2 carbapenemase, molecular characterization, epidemiology, and outcomes. Antimicrob Agents Chemother 52:1413–1418 [View Article][PubMed]
    [Google Scholar]
  13. Patel G., Huprikar S., Factor S. H., Jenkins S. G., Calfee D. P. 2008; Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 29:1099–1106 [View Article][PubMed]
    [Google Scholar]
  14. Poirel L., Héritier C., Tolün V., Nordmann P. 2004a; Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 48:15–22 [View Article][PubMed]
    [Google Scholar]
  15. Poirel L., Pham J. N., Cabanne L., Gatus B. J., Bell S. M., Nordmann P. 2004b; Carbapenem-hydrolysing metallo-β-lactamases from Klebsiella pneumoniae and Escherichia coli isolated in Australia. Pathology 36:366–367 [View Article][PubMed]
    [Google Scholar]
  16. Poirel L., Revathi G., Bernabeu S., Nordmann P. 2011; Detection of NDM-1-producing Klebsiella pneumoniae in Kenya. Antimicrob Agents Chemother 55:934–936 [View Article][PubMed]
    [Google Scholar]
  17. Queenan A. M., Bush K. 2007; Carbapenemases: the versatile β-lactamases. Clin Microbiol Rev 20:440–458 [View Article][PubMed]
    [Google Scholar]
  18. Smith Moland E., Hanson N. D., Herrera V. L., Black J. A., Lockhart T. J., Hossain A., Johnson J. A., Goering R. V., Thomson K. S. 2003; Plasmid-mediated, carbapenem-hydrolysing β-lactamase, KPC-2, in Klebsiella pneumoniae isolates. J Antimicrob Chemother 51:711–714 [View Article][PubMed]
    [Google Scholar]
  19. Song W., Bae I. K., Lee Y.-N., Lee C.-H., Lee S. H., Jeong S. H. 2007; Detection of extended-spectrum β-lactamases by using boronic acid as an AmpC β-lactamase inhibitor in clinical isolates of Klebsiella spp. and Escherichia coli. J Clin Microbiol 45:1180–1184 [View Article][PubMed]
    [Google Scholar]
  20. Song W., Suh B., Choi J. Y., Jeong S. H., Jeon E. H., Lee Y. K., Hong S. G., Lee K. 2009; In vivo selection of carbapenem-resistant Klebsiella pneumoniae by OmpK36 loss during meropenem treatment. Diagn Microbiol Infect Dis 65:447–449 [View Article][PubMed]
    [Google Scholar]
  21. Tenover F. C., Arbeit R. D., Goering R. V., Mickelsen P. A., Murray B. E., Persing D. H., Swaminathan B. 1995; Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33:2233–2239[PubMed]
    [Google Scholar]
  22. Walsh T. R. 2010; Emerging carbapenemases: a global perspective. Int J Antimicrob Agents 36:Suppl. 3S8–S14 [View Article][PubMed]
    [Google Scholar]
  23. Yang D., Guo Y., Zhang Z. 2009; Combined porin loss and extended spectrum β-lactamase production is associated with an increasing imipenem minimal inhibitory concentration in clinical Klebsiella pneumoniae strains. Curr Microbiol 58:366–370 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.037036-0
Loading
/content/journal/jmm/10.1099/jmm.0.037036-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error